SIX6

Chr 14AR

SIX homeobox 6

Also known as: MCOPCT2, ODRMD, OPTX2, Six9

NCBI Gene: 4990ENSG00000184302UniProt: O95475OMIM: 606326

The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in eye development. Defects in this gene are a cause of isolated microphthalmia with cataract type 2 (MCOPCT2). [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Optic disc anomalies with retinal and/or macular dystrophyMIM #212550
AR
UniProtOptic disk anomalies with retinal and/or macular dystrophy

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
24
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.59
LOEUF
LOF
Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.59LOEUF
pLI 0.518
Z-score 2.44
OE 0.19 (0.08–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.71Z-score
OE missense 0.83 (0.71–0.97)
117 obs / 140.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.19 (0.08–0.59)
0≤0.351.4
Missense OE?0.83 (0.71–0.97)
0≤0.61.4
Synonymous OE?0.85
0≤1.21.6
LoF obs/exp: 2 / 10.6Missense obs/exp: 117 / 140.8Syn Z: 0.94

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SIX6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients